骨钙素通过抑制脂肪组织炎症改善肥胖小鼠胰岛素敏感性
发布时间：2018-08-11 09:14
【摘要】：肥胖已经威胁到人类的健康,成为了众多疾病共同的危险因素,如心脑血管疾病,高血压,高血脂,糖尿病等,这与肥胖导致的慢性低度炎症反应相关,其中巨噬细胞向脂肪组织的浸润在炎症反应及胰岛素抵抗中发挥了重要作用,而巨噬细胞趋化蛋白1(MCP-1)则是导致巨噬细胞向脂肪组织浸润的重要因素之一。众多实验研究都致力于探索出有效的途径来减轻脂肪组织炎症反应,从而改善胰岛素抵抗,预防2型糖尿病的发生。骨钙素,是由成骨细胞分泌的一种蛋白,它能促使骨转化和骨合成,最新的研究发现它在调节糖及能量代谢方面也发挥了重要作用,从而能在一定程度上改善胰岛素抵抗,然而其相关机制尚不明确,本研究对不同剂量骨钙素对小鼠血糖、体脂量、胰岛素水平及肥胖相关的炎症反应指标等的影响作用及机制进行了深入的探讨,有望进一步扩大骨钙素的研究领域,同时在减轻肥胖相关的炎症反应方面获得新的突破。本实验选取C57BL/6小鼠,以高脂饮食喂养12周后,对肥胖小鼠每日腹腔注射骨钙素(30ng/kg或3ng/kg),对照组以等体积的生理盐水处理。测定各组小鼠体重、体脂、血清甘油三酯、游离脂肪酸变化;进行葡萄糖耐量试验、胰岛素耐量试验;免疫组化染色观察巨噬细胞向脂肪组织的浸润程度及巨噬细胞标志物CD68的蛋白表达量;实时荧光定量PCR检测巨噬细胞趋化蛋白1(MCP-1)及CD68mRNA表达。通过本实验研究,表明骨钙素(30ng/kg或者3ng/kg)处理4周后,与生理盐水处理的对照组相比,能有效降低高脂饮食小鼠的体重、体脂量、空腹胰岛素水平,改善其糖耐量异常和胰岛素抵抗。此外,在骨钙素(30ng/kg)治疗肥胖小鼠脂肪组织巨噬细胞的浸润减少,脂肪组织中MCP-1与CD68mRNA表达明显降低。该实验表明长期高脂饮食会使小鼠体重及脂肪含量明显增加,内脏脂肪组织出现炎症反应,产生了胰岛素抵抗,二者存在一定的相关性。骨钙素(30ng/kg)通过下调CD68和MCP-1的表达,抑制肥胖小鼠脂肪组织巨噬细胞聚集及MCP-1分泌,降低小鼠体重、体内脂肪含量,改善了肥胖小鼠的胰岛素敏感性。
[Abstract]:Obesity has threatened human health and become a common risk factor for many diseases, such as cardio-cerebrovascular disease, hypertension, hyperlipidemia, diabetes, and so on, which is associated with chronic low-grade inflammation caused by obesity. The infiltration of macrophages into adipose tissue plays an important role in inflammatory response and insulin resistance, and macrophage chemoattractant protein-1 (MCP-1) is one of the important factors leading to the infiltration of macrophages into adipose tissue. Many experimental studies have focused on finding effective ways to reduce inflammation in adipose tissue, improve insulin resistance and prevent type 2 diabetes. Osteocalcin, a protein secreted by osteoblasts that promotes bone transformation and bone synthesis, has been found to play an important role in regulating glucose and energy metabolism, thereby improving insulin resistance to some extent. However, the related mechanism of osteocalcin was not clear. The effects and mechanisms of different doses of osteocalcin on blood glucose, body fat, insulin level and inflammatory response indexes related to obesity in mice were studied. It is expected to further expand the research field of osteocalcin and make a new breakthrough in reducing the inflammatory response related to obesity. In this experiment, C57BL/6 mice were fed with high-fat diet for 12 weeks. The obese mice were given intraperitoneal injection of osteocalcin (30ng/kg or 3ng/kg) daily, and the control group was treated with normal saline of the same volume. Body weight, body fat, serum triglyceride, free fatty acid were measured, glucose tolerance test and insulin tolerance test were performed. The infiltration of macrophages into adipose tissue and the protein expression of macrophage marker CD68 were observed by immunohistochemical staining, and the expression of chemotactic protein 1 (MCP-1) and CD68mRNA in macrophages were detected by real-time fluorescence quantitative PCR. The results showed that after 4 weeks of treatment with 30ng/kg or 3ng/kg, compared with the control group treated with normal saline, the body weight, body fat and fasting insulin level of mice fed with high fat diet were significantly decreased, and compared with the control group treated with normal saline, osteocalcin (30ng/kg or 3ng/kg) could effectively reduce the body weight, body fat and fasting insulin level. Improve glucose tolerance and insulin resistance. In addition, osteocalcin (30ng/kg) treatment decreased the infiltration of macrophages in adipose tissue and the expression of MCP-1 and CD68mRNA in adipose tissue of obese mice. The results showed that long-term high-fat diet could significantly increase the body weight and fat content of mice, and the visceral adipose tissue appeared inflammatory reaction, which resulted in insulin resistance, and there was a certain correlation between them. Osteocalcin (30ng/kg) can down-regulate the expression of CD68 and MCP-1, inhibit macrophage aggregation and MCP-1 secretion in adipose tissue of obese mice, decrease body weight and fat content, and improve insulin sensitivity in obese mice.
【学位授予单位】：河北北方学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.2;R587.1
本文编号：2176558
[Abstract]:Obesity has threatened human health and become a common risk factor for many diseases, such as cardio-cerebrovascular disease, hypertension, hyperlipidemia, diabetes, and so on, which is associated with chronic low-grade inflammation caused by obesity. The infiltration of macrophages into adipose tissue plays an important role in inflammatory response and insulin resistance, and macrophage chemoattractant protein-1 (MCP-1) is one of the important factors leading to the infiltration of macrophages into adipose tissue. Many experimental studies have focused on finding effective ways to reduce inflammation in adipose tissue, improve insulin resistance and prevent type 2 diabetes. Osteocalcin, a protein secreted by osteoblasts that promotes bone transformation and bone synthesis, has been found to play an important role in regulating glucose and energy metabolism, thereby improving insulin resistance to some extent. However, the related mechanism of osteocalcin was not clear. The effects and mechanisms of different doses of osteocalcin on blood glucose, body fat, insulin level and inflammatory response indexes related to obesity in mice were studied. It is expected to further expand the research field of osteocalcin and make a new breakthrough in reducing the inflammatory response related to obesity. In this experiment, C57BL/6 mice were fed with high-fat diet for 12 weeks. The obese mice were given intraperitoneal injection of osteocalcin (30ng/kg or 3ng/kg) daily, and the control group was treated with normal saline of the same volume. Body weight, body fat, serum triglyceride, free fatty acid were measured, glucose tolerance test and insulin tolerance test were performed. The infiltration of macrophages into adipose tissue and the protein expression of macrophage marker CD68 were observed by immunohistochemical staining, and the expression of chemotactic protein 1 (MCP-1) and CD68mRNA in macrophages were detected by real-time fluorescence quantitative PCR. The results showed that after 4 weeks of treatment with 30ng/kg or 3ng/kg, compared with the control group treated with normal saline, the body weight, body fat and fasting insulin level of mice fed with high fat diet were significantly decreased, and compared with the control group treated with normal saline, osteocalcin (30ng/kg or 3ng/kg) could effectively reduce the body weight, body fat and fasting insulin level. Improve glucose tolerance and insulin resistance. In addition, osteocalcin (30ng/kg) treatment decreased the infiltration of macrophages in adipose tissue and the expression of MCP-1 and CD68mRNA in adipose tissue of obese mice. The results showed that long-term high-fat diet could significantly increase the body weight and fat content of mice, and the visceral adipose tissue appeared inflammatory reaction, which resulted in insulin resistance, and there was a certain correlation between them. Osteocalcin (30ng/kg) can down-regulate the expression of CD68 and MCP-1, inhibit macrophage aggregation and MCP-1 secretion in adipose tissue of obese mice, decrease body weight and fat content, and improve insulin sensitivity in obese mice.
【学位授予单位】：河北北方学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R589.2;R587.1
【参考文献】
相关期刊论文 前5条
1 刘冬梅;刘建民;;骨钙素对糖代谢的调控作用[J];中华骨质疏松和骨矿盐疾病杂志;2015年02期
2 戴小宇;滕华建;徐兴全;姚尧;葛启婷;蒋青;;骨钙素调节糖代谢的研究进展[J];中国病理生理杂志;2013年05期
3 郭晓强;;骨钙素:一种重要的能量代谢调节激素[J];生命科学;2011年01期
4 李新;袁莉;李进;李海玲;程梭梭;;长期高脂喂养大鼠胰岛功能改变与胰岛炎症反应有关[J];中国病理生理杂志;2009年05期
5 崔丽娟;都健;;脂联素与炎症及胰岛素抵抗关系的研究进展[J];国际内分泌代谢杂志;2006年S1期
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